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Henry Liu-Log
Link to Henry Liu-Final


Assignment 1: 25 Chemical Properties
Chemical: 3-Methylpyridazine
CSID: 66816 ChemSpider Link
SMILES: n1nc(ccc1)C
CAS: 1632-76-4

Boiling Point:
212.5 deg C LookChem *DONE
213-214 deg C Alfa Aesar *DONE
214 deg C Sigma-Aldrich *DONE
215 deg C Tokyo Chemical Industry UK Ltd *DONE
417 deg F Santa Cruz Biotechnology MSDS *DONE

Flash Point:
87 deg C Tokyo Chemical Industry UK Ltd *DONE
87.78 deg C Wolfram Alpha *DONE
87.8 deg C LookChem *DONE
88 deg C Sigma-Aldrich MSDS *DONE
190 deg F Santa Cruz Biotechnology MSDS *DONE

Refractive Index:
1.503 Chemnet *DONE
1.5140 Alfa Aesar *DONE
1.514-1.516 Chem Exper *DONE

Vapor Pressure:
0.25 mmHg Wolfram Alpha *DONE
0.25099 mmHg Chemspider Predictor *DO NOT USE predicted value yet

Specific Gravity:
1.05 g/mL Tokyo Chemical Industry UK Ltd *DONE
1.021 g/mL LookChem *DONE
1.030 g/mL Alfa Aesar *DONE
1.031 g/mL Santa Cruz Biotechnology MSDS *DONE
1.0491 g/mL (@20 deg C) VWR International, LLC *DONE


Chemical: ethyl pentafluoropropionate
CSID: 61245 Chemspider Link
SMILES: FC(F)(C(=O)OCC)C(F)(F)F
CAS: 426-65-3

Boiling Point:
73-74 deg C Alfa Aesar
75-76 deg C Sigma-Aldrich *DONE
76 deg C Tokyo Chemical Industry UK Ltd

Flash Point:
33 deg F Alfa Aesar
2 deg C Sigma-Aldrich MSDS
35 deg F Chemical Book *DONE

Inputted into "chem info sheet 2012" on 10/7/2012
UPDATE: fixed first round of errors on 10/9/201; last updated: 11/29/2012 (4 properties for ethyl pentafluoropropionate are still pending corrections)




Assignment 2: Summary of Research Article
11/29/2012

Research topic: A brief review of 8-oxoguanine in signaling damaged DNA and how its chemical/structural properties affect its repair mechanism.
CHEMICAL: 8-oxoguanine
CSID: 106574
Chemspider Link: http://www.chemspider.com/106574
SMILES: c12=NC(=O)N=c1[nH]c(nc2=O)N
CAS: 5614-64-2

PubMed article: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=65154&loc=ec_rcs

Wikipedia: http://en.wikipedia.org/wiki/8-oxoguanine
"8-Oxoguanine (8-hydroxyguanine, 8-oxo-Gua, or OH^(8)Gua) is one of the most common DNA lesions resulting from reactive oxygen species and can result in a mismatched pairing with Adenine resulting in G to T and A to C substitutions in the genome. In humans, it is primarily repaired by the DNA glycosylase OGG1. It can be caused by ionizing radiation, in connection with oxidative metabolism."

RESEARCH ARTICLE: Mutagenesis by 8-oxoguanine: an enemy within
Review paper
Authors: Arthur P. Grollman, Masaaki Moriya
Department of Pharmacological Sciences, State University of New York at Stony Brook, Stony Brook, NY 11794-8651, USA
Cell Press: Trends in Genetics Volume 9, Issue 7, July 1993, Pages 246–249

DOI: http://dx.doi.org/10.1016/0168-9525(93)90089-Z

ABSTRACT: The presence of reactive oxygen species in cells ensures that the oxidatively damage base 8-oxoguanine will be generated at high frequency in the DNA of all living organisms. DNA damage threatens genomic integrity: enzymes have evolved that protect prokaryotes and eukaryotes from the mutagenic effect of this ubiquitous lesion.

Summary (bullet points by paragraph; I fully acknowledge that I went over the one to two sentences per paragraph suggestion.):

INTRO
  • Reactive oxygen species (ROS) both prevalent in nature and inherently produced are toxic to living organisms' DNA. There are many host biochemical molecules and enzymes that counteract the damage caused by ROS, but thymine glycol and 8-oxoguanine are two modified DNA bases used to quantify the extent of host oxidative damage.
  • While ROS are byproducts of cellular metabolism, they can be formed as a result of exogenous influences such as ionizing radiation and by xenobiotics. 8-oxoguanine has been used as a indicator for deleterious effects of ROS such as cancer and aging.
  • Deoxyguanosine is easily oxidized to 8-oxodeoxyguanosine (8-oxodG). About 1/100,000 guanine resides in human DNA is oxidized at C-8 leading to endogenous DNA "miscoding".

EFFECTS
  • 8-oxodG miscodes by incorporating dAMP and dCMP opposite 8-oxodG in vitro. DNA replication polymerases (pol [alpha], pol [delta] and pol III) incorporated dAMP opposite 8-oxodG, while DNA replication polymerases (pol I and pol [beta]) incorporated dCMP opposite 8-oxodG.
  • The 3'->5' exo-nucleolytic proofreading of pol I and pol III does not fix the incorrect dAMP:8-oxodG pairing. Incorrectly paired damaged bases generally are not extended efficiently in DNA polymerases, however 8-oxodG:dA is an exception. The geometry of 8-oxodG(syn):dA(anti) shields the 3' end from exonucleolytic proofreading.
  • Studies were performed with plasmid vectors containing a single lesion to determine the mutational frequency and specificity of 8-oxodG. The majority of mutations were G:C->T:A transversions. Mutational frequencies were <5%, revealing 8-oxodG to be weakly mutagenic in vivo.
  • Because dGTP can be attacked by ROS, 8-oxodGTP is present in the dNTP pool. DNA polymerases pair 8-oxodGMP with dC or dA on the template DNA strand, forming A:T->C:G transversions.

MECHANISMS
  • Because ROS is ubiquitous both exogenously and endogenously, all living organisms must develop functional enzymes and repair mechanisms to prevent the mutagenic effects of this DNA lesion.
  • 8-oxodGTP pairs with almost equal efficiency to dC and dA, generating a high frequency of A:T->C:G transversions. The first level of protection is a nucleotide triphosphatase that hydrolyses 8-oxodGTP, preventing it from being incorporated in any proliferating DNA strands.
  • A second level of protection involves 8-oxoguanine DNA glycosylase (formamidopyrimidine DNA glycosylase or the Fpg protein). This enzyme removes 8-oxoguanine from DNA where the lesion is paired with dC, repairing the base pair. The glycosylase is less active on 8-oxodG:dA pairing, which is the favored pairing during DNA replication. 8-oxoguanine DNA glycosylase defends against mutagenesis by promoting G:C->T:A transversions.
  • A third level of protection occurs when 8-oxodG is failed to be repaired by 8-oxoguanine DNA glycosylase. Downstream enzymatic removal repairs the misincorporated adenine, but full repair of the lesion is not effected until dCMP is inserted.
  • For different strains of E. coli, there are consequences of the different levels of protection. MutT strains are deficient in adenine DNA glycosylase and have G:C->T:A mutations. The mutT overproduces 8-oxoguanine DNA glycosylase, suggesting that 8-oxodG:dA is the natural substrate for this enzyme. A mutM mutY double mutation work together to protect against G:C->T:A mutations.
  • Evidence shows that the mutY gene in E. coli produce an enzyme that directly reduce the frequency of G:C->T:A mutations in vivo.
  • Misincorporated adenine residues are removed by adenine DNA glycosylase, creating an abasic site. This site is incised by AP endonuclease activity and the gap is filled by pol I to pair dCMP opposite 8-oxodG. This produces the substrate for 8-oxoguanine DNA glycosylase, which can restore the natural base pairing.
  • Mammalian counterparts of the products of the E. coli genes mutM, mutY and mutT have been identified and it appears that an analogous defense system operates in mammalian cells.

CONFORMATION
  • Deoxyguanosine form altered electronic and conformational properties upon oxidation at C-8; the syn and anti forms of 8-oxodG form an equilibrium, with the syn conformation being energetically preferred. In the syn form the modified dNTP is paired with dA. 8-oxodG positioned in the template strand may assume syn or anti conformations, depending on the dNMP inserted, suggesting steric repulsion between the 8-oxo and deoxyribose moieties in 8-oxodG(anti):dC(anti) is stabilized by a third hydrogen bond.
  • Formation of 8-oxodG(syn):dA(anti) induces mutagenesis during DNA replication. The steric positions of the hydrogen bonds in the major and minor grooves of the DNA affects its recognition by DNA polymerases, which affects binding and incision by DNA glycosylases during DNA repair.
  • Three DNA structures are considered: 8-oxodG(syn) opposite dA(anti), 8-oxodG(anti) opposite dC(anti), and 8-oxodG(syn) opposite an abasic site. The first two structures represent natural substrates for 8-oxoguanine DNA glycosylase and adenine DNA glycosylase, respectively; the third is an intermediate in 8-oxodG repair. When 8-oxodG is anti, the carbonyl group at C-8 resides in the major groove and the exocyclic amino group is found in the minor groove. In theory, DNA glycosylase could distinguish between two 8-oxopurines by binding the exocyclic amino group of 8-oxodG; however, the enzyme is required to make contact with structures in the minor and major grooves. A more plausible hypothesis involves the recognition mechanism of the C-6 and C-8 carbonyl functions of 8-oxodG(anti).
  • 8-oxodG(syn):dA(anti) is resistant to 8-oxoguanine DNA glycosylase and is a natural substrate for adenine DNA glycosylase. Adenine glycosylase inhibits 8-oxoguanine DNA glycosylase, suggesting that both enzymes compete for the same binding site. The 8-oxo group is not involved in the DNA site recognition process. Pressumably, adenine DNA glycosylase encounters hydrogen bond donors and/or acceptors common to guanine(syn) and 8-oxoguanine(syn), in conjunction with the exocyclic amino function of dA(anti). Further structure-activity analysis will be required to determine the relationship between the binding of DNA glycosylase and the repair effects of 8-oxoguanine.